A PDE3A mutation in familial hypertension and brachydactyly syndrome

Boda, Hiroko; Uchida, Hidetoshi; Takaiso, Nobue; Ouchi, Yuya; Fujita, Naoko; Kuno, Asami; Hata, Tadayoshi; Nagatani, Arisa; Funamoto, Yuri; Miyata, Masafumi; Yoshikawa, Tetsushi; Kurahashi, Hiroki; Inagaki, Hidehito

doi:10.1038/jhg.2016.32

Cited by 34 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 Three families of PDEs (PDE1-3) have affinities for both cAMP and cGMP, 5 and recently both PDE2A and PDE3A have been implicated in the pathogenesis of hypertension. 6,7 We confirmed the presence of PDE2A and demonstrated pharmacologically a role for PDE3 in PGSNs. Given that PDE2A is activated by cGMP, and PDE3 is inhibited by cGMP, we suggest that the differential cAMP responses to cGMP observed in healthy versus diseased neurons, may arise as a result of altered PDE2/3 activity (Fig.…”

supporting

confidence: 59%

See 1 more Smart Citation

Impaired cAMP-cGMP cross-talk during cardiac sympathetic dysautonomia

2016

View full text Add to dashboard Cite

supporting

confidence: 59%

“…8 Another possibility is that cAMP-hydrolysing PDE isoforms (e.g. PDE 4,7,8) are upregulated in diseased PGSNs, facilitating excessive cAMP hydrolysis following physiological stimuli. However, there is no compelling evidence to date that these PDE isoforms are present in sympathetic neurons.…”

mentioning

confidence: 99%

Impaired cAMP-cGMP cross-talk during cardiac sympathetic dysautonomia

2016

View full text Add to dashboard Cite

“…PDEs are involved in different stages of advanced cardiac diseases. PDE1-3 hydrolyze cAMP and cGMP, and both PDE2A and PDE3A have been implicated in the pathogenesis of hypertension (6,27). Some report that the activity of PDE2A towards the hydrolysis of cAMP is relatively low compared with cGMP (28), although it still contributes to the regulation of cardiac L-type calcium channel (I CaL ) activity, where it inhibits the activation of I CaL by reducing cAMP concentration after being stimulated by cGMP (29).…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity

Liu¹,

Li²,

Hao³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Elevated levels of brain natriuretic peptide (BNP) are regarded as an early compensatory response to cardiac myocyte hypertrophy, although exogenously administered BNP shows poor clinical efficacy in heart failure and hypertension. We tested whether phosphodiesterase 2A (PDE2A), which regulates the action of BNP-activated cyclic guanosine monophosphate (cGMP), was directly involved in modulating Ca2+ handling from stellate ganglia (SG) neurons and cardiac norepinephrine (NE) release in rats and humans with an enhanced sympathetic phenotype. SG were also isolated from patients with sympathetic hyperactivity and healthy donor patients. PDE2A activity of the SG was greater in both spontaneously hypertensive rats (SHRs) and patients compared with their respective controls, whereas PDE2A mRNA was only high in SHR SG. BNP significantly reduced the magnitude of the calcium transients and ICaN in normal Wistar Kyoto (WKY) SG neurons, but not in the SHRs. cGMP levels stimulated by BNP were also attenuated in SHR SG neurons. Overexpression of PDE2A in WKY neurons recapitulated the calcium phenotype seen in SHR neurons. Functionally, BNP significantly reduced [3H]-NE release in the WKY rats, but not in the SHRs. Blockade of overexpressed PDE2A with Bay 60-7550 or overexpression of catalytically inactive PDE2A reestablished the modulatory action of BNP in SHR SG neurons. This suggests that PDE2A may be a key target in modulating the action of BNP to reduce sympathetic hyperactivity.

show abstract

“…More recently, the case of a young patient with PHP1B who had juvenile renin-dependent hypertension has been reported 238 . A direct link between the cAMP signal transduction pathway and hypertension has been demonstrated by the finding of PDE3A mutations in families with autosomal dominant hypertension and brachydactyly type E syndrome 21,239 , and the mechanism underlying hypertension in these patients is thought to be related to increased peripheral vascular resistance due to vasoconstriction. Recommendations 3.27.…”

Section: Obesity and Other Metabolic Issuesmentioning

confidence: 99%

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international consensus statement

Mantovani¹,

Lecumberri²,

Baştepe³

et al. 2018

EJEA

View full text Add to dashboard Cite

Pseu do hy popar ath yroi dism (PHP) and related disorders are associated with a spectrum of abnormal physical characteristics as well as neurocognitive and endocrine abnormalities that are caused primarily by molecular defects that impair hormonal signalling via receptors that are coupled, through the α-subunit of the stimulatory G protein (G s α), to activation of adenylyl cyclase (Fig. 1). 6,7,20,48 * Abstract | This Consensus Statement covers recommendations for the diagnosis and management of patients with pseu do hy popar ath yroi dism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency , hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.

show abstract

A PDE3A mutation in familial hypertension and brachydactyly syndrome

Cited by 34 publications

References 15 publications

Impaired cAMP-cGMP cross-talk during cardiac sympathetic dysautonomia

Impaired cAMP-cGMP cross-talk during cardiac sympathetic dysautonomia

Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international consensus statement

Contact Info

Product

Resources

About